Nrldl, an Important Circadian Pathway Regulatory Gene, Is Suppressed By Cigarette Smoke in Murine Lungs

作者：Vasu Vihas T^*; Cross Carroll E; Gohil Kishorchandra

来源：Integrative Cancer Therapies, 2009, 8(4): 321-328.

DOI：10.1177/1534735409352027

• Nrldl
• Rev-erb-alpha
• C57BL6 mice strain
• AJ mice strain
• lungs
• cigarette smoke
• gene expression profiling
• chronobiology

Nuclear receptor subfamily I, group D member I (Nrldl), also known as Rev-erb-alpha, belongs to the family of "orphan receptors" and functions as a member of clock gene family. In addition to being an important member of clock circuitry, Nrldl, also regulates cell proliferation, lipid metabolism,and inflammation and is also touted as a tumor suppressor. Our focus on Nrldl was stimulated by data from a genome-wide search for mRNA correlates of cigarette smoke (CS) sensitive-whole smoke (WS) and filtered smoke (FS)-lung transcriptomes in tumor-resistant C57BL6 and tumor-susceptible AJ mice strains. Differential analysis of similar to 15 000 genes using Affymetrix 430A 2.0 high-density oligonucleotide arrays identified modulation of genes related to circadian pathways by CS in lungs of both mouse strains. Nrldl expression was downregulated by both WS and FS irrespective of mouse strain as compared to respective air-breathing controls. WS was more effective than FS on decreasing Nrldl expression. The present data suggest that transcriptional regulation of Nrldl by CS may affect circadian rhythmicity and thus may play a complementary role in CS-induced lung respiratory tract pathobiology and/or lung tumorigenesis.

• 出版日期2009-12